Devices and methods to simulate an ocular environment

ABSTRACT

Methods and devices used to simulate the use of an ophthalmic lens contained in an ocular environment are disclosed herein.

RELATED APPLICATION

This application is a non-provisional filing of a provisionalapplication, U.S. Ser. No. 60/855,433, filed on Oct. 31, 2006.

FIELD OF THE INVENTION

This invention related to devices and methods simulate an ocularenvironment to enable the testing of ophthalmic lens.

BACKGROUND

Most diseases of the eye are treated with topical ophthalmic solutionscontaining pharmaceutical agents. It has been postulated that deliveryand efficacy of these agents would be greatly increased if the agentswere incorporated in ophthalmic lenses and those lenses were used asdrug delivery devices. These agents may be added to the ophthalmiclenses by a variety of methods including soaking the agent into a formedlens, adding the agent to the formulation of the lens prior to itsformation and the like. Others have postulated methods of testing theuptake and discharge rates of such pharmaceutical agents to and from theophthalmic lenses. These methods include placing ophthalmic lenses insolutions and monitoring the concentration of the pharmaceutical agentover time. Even though these methods work, due to the volume of solutionused in the test, the conditions do not mimic the conditions that anophthalmic lens is exposed to when inserted into an ocular environment.

In an ocular environment, very small volumes of tear fluid pass over thelens during its use. Therefore it would be beneficial if one could mimicthose conditions to test the performance of ophthalmic lenses. This needis met by the following invention

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a perspective drawing of a male mold.

FIG. 2 illustrates a perspective drawing of a female mold.

FIG. 3 illustrates a close up cross-sectional drawing of the matedapparatus.

FIG. 4 illustrates a perspective drawing of a male mold.

FIG. 5 illustrates a perspective drawing of a female mold.

FIG. 6 illustrates a cross-sectional drawing of the mated apparatus.

FIG. 7 illustrates a close up cross-sectional drawing of the matedapparatus.

DETAILED DESCRIPTION OF THE INVENTION

This invention includes an apparatus for testing an ophthalmic lenscomprising a male mold and a female mold,

-   -   wherein said male mold comprises a convex testing surface, an        outer male surface, male seating ridge extending from the        perimeter of the convex testing surface, and an aperture        extending from said outer male surface to said convex testing        surface,    -   wherein said female mold comprises an outer female surface a        concave testing surface, female seating ridge extending from the        perimeter of the concave testing surface, and an aperture        extending from said concave testing surface to said outer female        surface,    -   wherein when the male mold and the female mold are mated, the        male seating ridge sits on the female seating ridge and creates        a testing area between the male convex testing surface and the        female concave testing surface.        An embodiment of the invention is illustrated in the following        figures.

FIG. 1, a perspective drawing of a male mold 100, contains convextesting surface 120, aperture 160, and, male seating ridge 180. FIG. 2,a perspective drawing of a female mold 200, contains concave testingsurface 220, aperture 260, and female seating ridge 280. FIG. 3, a closeup cross section of mated apparatus, where the mated convex testingsurface 120 and concave testing surface 220, define the testing area 300between those surfaces. Preferably the convex and concave testingsurfaces are of a size and shape to mimic the shape of the eye and aneyelid. Testing area 300 is large enough to hold an ophthalmic lens (notshown) and a volume of solution. It is preferred that the testing areabe sized to house an ophthalmic lens and about 50 μL to about 500 μL ofsolution, more preferably, about 100 μL to about 400 μL of solution,most preferably about 200 μL of solution.

The convex or concave testing surfaces of the apparatus may containgrooves that provide pathways for the small volumes of solutions to passover the surfaces of ophthalmic lenses contained in the testing area.These grooves may be in any number or orientation, but preferably aconvex or concave testing surface contains at least one latitudinalgroove and one radial groove. It is preferred that such groovesintersect at a point on the convex or concave testing surface. In anembodiment of the invention is illustrated in the following figures boththe concave and the convex surfaces contain radial and latitudinalgrooves.

FIG. 4, a perspective drawing of a male mold 10, contains convex testingsurface 12, four radial grooves 14, aperture 16, male seating ridge 18,and six concentric latitudinal grooves 19. FIG. 5, a perspective drawingof a female mold 20, contains concave testing surface 22, four radialgrooves, 24, aperture 26, female seating ridge 28, and nine concentriclatitudinal grooves 29. The radial grooves on the convex testing surfaceintersect with the latitudinal grooves so as to allow solutions thatflow through the apertures, to more easily flow to the entire convextesting surface. This structural arrangement exists on the concavetesting surface as well. Each testing surface may contain the same ordifferent numbers of radial grooves. It is preferred that each testingsurface contain contains at least two radial grooves, more preferablythree radial grooves, most preferably four radial grooves. With respectto latitudinal grooves, the number of these grooves on each testingsurface may be the same or different. It is preferred that each testingsurface contain contains at least four latitudinal grooves, morepreferably at least five latitudinal grooves, most preferably at leasteight latitudinal grooves. The outer male and female surfaces may be thesame or different shapes. In one embodiment of the invention (notillustrated) the outer male surface is concave and the outer femalesurface is convex. Preferably, the convex and concave testing surfacesare of a size and shape to mimics the shape of an eye and an eyelid.

FIG. 6, a cross section of the mated apparatus, with male mold 10,female mold 20, male outer surface 13, female outer surface 23, maleseating ridge 18, and female seating ridge 28. As illustrated in FIG. 6,aperture 16 extends from male outer surface 13 to the convex testingsurface 12 to the testing area not shown. Further, aperture 26 extendsfrom concave testing surface 22 to outer female surface 23. FIG. 7, aclose up cross section of mated apparatus, where the mated convextesting surface 12 and concave testing surface 22, define the testingarea 30 those surfaces. Testing area 30 is large enough to hold anophthalmic lens (not shown) and a volume of solution. It is preferredthat the testing area be sized to house an ophthalmic lens and about 50μL to about 500 μL of solution, more preferably, about 100 μL to about400 μL of solution, most preferably about 200 μL of solution.

The apparatus of the invention may be prepared from durablethermoplastic materials, such as thermoplastic resins, polyolefins, andthermoplastic polyesters. Examples of such materials include but are notlimited to low medium, medium and high density polypropylene,polyethylene and co-polymers thereof, poly-4-methylpentene, fluorinatedethylene propylene copolymers, ethylene fluoroethylene copolymers,polyacetal resins, polacrylether, polyarylether sulfones, nylons, andthe like. The apparatus may be prepared by injection moldingthermoforming and the like.

Further the invention includes a method of testing the diffusion rate ofan ophthalmic device comprising a pharmaceutical agent, wherein themethod comprises the steps of

-   -   (a) placing an ophthalmic lens comprising a pharmaceutical agent        in the testing area of an apparatus comprising a male mold and a        female mold,        -   wherein said male mold comprises a convex testing surface an            outer male surface, male seating ridge extending from the            perimeter of the convex testing surface, and an aperture            extending from said outer male surface to said convex            testing surface,        -   wherein said female mold comprises an outer female surface a            concave testing surface, female seating ridge extending from            the perimeter of the concave testing surface, and an            aperture extending from said concave testing surface to said            outer female surface,        -   wherein when the male mold and the female mold are mated,            the male seating ridge sits on the female seating ridge and            creates a testing area between the male convex testing            surface and the female concave testing surface.    -   (b) adding a solution to the aperture of the male mold from the        outer male surface, and    -   (c) monitoring the solution that emerges from the aperture of        the outer female surface to determine the presence or absence of        the pharmaceutical agent.        As used herein the term male mold, female mold, radial groove,        latitudinal groove, testing area convex testing surface, and        concave testing surface are as described above.

As used herein, “pharmaceutical agents refers to pharmaceutical ornutraceutical compounds used to treat conditions of the eye, and suchcompound degrade in the presence of oxygen and certain transitionmetals. Examples of pharmaceutical compounds include antihistamines,antibiotics, antibacterial agents, antiviral agents, antifungal agents,analgesics, anesthetics, antiallergeneic agents, mast cell stabilizers,steroidal and non-steroidal anti-inflammatory agents, angiogenesisinhibitors; antimetabolites, fibrinolytics, neuroprotective drugs,angiostatic steroids, mydriatics, cyclopegic mydriatics; miotics;vasoconstrictors; vasodilators, anticlotting agents; anticancer agents,antisense agents, immunomodulatory agents, carbonic anhydraseinhibitors, integrin antabonistsl; cyclooxygenase inhibitors, VEGFantagonists; immunosuppressant agents and the like. Particularly,examples of pharmaceutical compounds include but are not limited toacrivastine, antazoline, astemizole, azatadine, azelastine, buclizine,bupivacaine, cetirizine, clemastine, cyclizine, cyproheptadine,ebastine, emedastine, ephedrine, eucatropine, fexofenadine, homatropine,hydroxyzine, ketotifen, levocabastine, levoceterizine, lomefloxacin,meclizine, mepivacaine, mequitazine, methdilazine, methapyrilene,mianserin, naphazoline norastemizole, norebastine, ofloxacin,oxymetazoline, pheniramine, phenylephrine, physostigmine, picumast,promethazine, scopolamine, terfenadine, tetrahydrozoline,thiethylperazine, timolol, trimeprazine, triprolidine, pharmaceuticallyacceptable salts and mixtures thereof. Preferred pharmaceuticalcompounds include acrivatine, antazoline, astemizole, azatadine,azelastine, clemastine, cyproheptadine, ebastine, emedastine,eucatropine, fexofenadine, homatropine, hydroxyzine, ketotife,levocabastine, levoceterizine, meclizine, mequitazine, methdialazine,methapyrilene, norastemizole, norebastine, oxymetazoline, physootigmine,picumast, promethazine, scopolamine, terfenadine, tetrahyerozoline,fimilol, trimeprazine, triprolidine, and pharmaceutically acceptablesalts thereof. Particularly preferred pharmaceutical compounds includephenarimine, ketotifen, ketotifen fumarate nor ketotifen fumarate,11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine-3-carboxaldehyde(CAS# 147084-10-4), olapatadine and mixtures thereof. More particularlypreferred pharmaceutical compounds include ketotifen fumarate,11-dihydro-11-(1-methyl-4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine-3-carboxaldehyde(CAS# 147084-10-4) and mixtures thereof.

Examples of nutraceutical compounds include vitamins and supplementssuch as vitamins A, D, E, lutein, zeaxanthin, lipoic acid, flavonoids,ophthalmicially compatible fatty acids, such as omega 3 and omega 6fatty acids, combinations thereof, combinations with pharmaceuticalcompounds and the like. The methods of the invention may be used todetect the discharge rate (or uptake rate) of ophthalmic lensescontaining about 8 μg or more of pharmaceutical agent. Preferably, thedischarge rate for ophthalmic lenses that contain about 8 μg to about 90μg, more preferably about 10 μg to about 40 μg, more preferably about 10μg to about 25 μg may be determined by the methods of this invention.

As used herein, “ophthalmic lens” refers to a device that resides in oron the eye. These devices can provide optical correction or may becosmetic. Ophthalmic lenses include but are not limited to soft contactlenses, intraocular lenses, overlay lenses, ocular inserts, and opticalinserts. The preferred lenses of the invention are soft contact lensesmade from silicone elastomers or hydrogels, which include but are notlimited to silicone hydrogels, and fluorohydrogels. Soft contact lensformulations are disclosed in U.S. Pat. No. 5,710,302, WO 9421698, EP406161, JP 2000016905, U.S. Pat. No. 5,998,498, U.S. Pat. No. 6,087,415,U.S. Pat. No. 5,760,100, U.S. Pat. No. 5,776,999, U.S. Pat. No.5,789,461, U.S. Pat. No. 5,849,811, and U.S. Pat. No. 5,965,631. Theforegoing references are hereby incorporated by reference in theirentirety. The particularly preferred ophthalmic lenses of the inventionsare known by the United States Approved Names of acofilcon A, alofilconA, alphafilcon A, amifilcon A, astifilcon A, atalafilcon A, balafilconA, bisfilcon A, bufilcon A, comfilcon, crofilcon A, cyclofilcon A,darfilcon A, deltafilcon A, deltafilcon B, dimefilcon A, drooxifilcon A,epsifilcon A, esterifilcon A, etafilcon A, focofilcon A, genfilcon A,govafilcon A, hefilcon A, hefilcon B, hefilcon D, hilafilcon A,hilafilcon B, hioxifilcon B, hioxifilcon C, hixoifilcon A, hydrofilconA, lenefilcon A, licryfilcon A, licryfilcon B, lidofilcon A, lidofilconB, lotrafilcon A, lotrafilcon B, mafilcon A, mesifilcon A, methafilconB, mipafilcon A, nelfilcon A, netrafilcon A, ocufilcon A, ocufilcon B,ocufilcon C, ocufilcon D, ocufilcon E, ofilcon A, omafilcon A, oxyfilconA, pentafilcon A, perfilcon A, pevafilcon A, phemfilcon A, polymacon,silafilcon A, siloxyfilcon A, tefilcon A, tetrafilcon A, trifilcon A,vifilcon, and xylofilcon A. More particularly preferred ophthalmiclenses of the invention are genfilcon A, lenefilcon A, comfilcon,lotrafilcon A, lotraifilcon B, and balafilcon A. The most preferredlenses include etafilcon A, nelfilcon A, hilafilcon, vifilcon, andpolymacon.

The “solutions” that are used in methods of this invention may bewater-based solutions. Solutions that mimic natural tear film arepreferred. Typical solutions include, without limitation, salinesolutions, other buffered solutions, and deionized water. The preferredaqueous solution is deioinized water or saline solution containing saltsincluding, without limitation, sodium chloride, sodium borate, sodiumphosphate, sodium hydrogenphosphate, sodium dihydrogenphosphate, or thecorresponding potassium salts of the same. These ingredients aregenerally combined to form buffered solutions that include an acid andits conjugate base, so that addition of acids and bases cause only arelatively small change in pH. The buffered solutions may additionallyinclude 2-(N-morpholino)ethanesulfonic acid (MES), sodium hydroxide,2,2-bis(hydroxymethyl)-2,2′,2″-nitrilotriethanol,n-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid, citric acid,sodium citrate, sodium carbonate, sodium bicarbonate, acetic acid,sodium acetate, ethylenediamine tetraacetic acid and the like andcombinations thereof.

As used herein “monitoring” refers to methods of analyzing the solutionto determine the concentration of pharmaceutical agent in the solution.Examples of such detecting methods include but are not limited to HPLC,UV Spectormeters and the like.

Still further the invention includes, a method of measuring the uptakerate of a pharmaceutical agent to an ophthalmic lens, wherein the methodcomprises the steps of

-   -   (a) placing an ophthalmic lens in the testing area of an        apparatus comprising a male mold and a female mold,        -   wherein said male mold comprises a convex testing surface an            outer male surface, male seating ridge extending from the            perimeter of the convex testing surface, and an aperture            extending from said outer male surface to said convex            testing surface,        -   wherein said female mold comprises an outer female surface a            concave testing surface, female seating ridge extending from            the perimeter of the concave testing surface, and an            aperture extending from said concave testing surface to said            outer female surface,        -   wherein when the male mold and the female mold are mated,            the male seating ridge sits on the female seating ridge and            creates a testing area between the male convex testing            surface and the female concave testing surface.    -   (b) adding a solution comprising a pharmaceutical agent to the        aperture of the male mold from the outer male surface, and    -   (c) monitoring the solution that emerges from the aperture of        the outer female surface to determine the presence or absence of        the pharmaceutical agent.        As used herein the term male mold, female mold, radial groove,        latitudinal groove, testing area convex testing surface, concave        testing surface, pharmaceutical agent, ophthalmic lens, solution        and monitoring are as described above.

There are other circumstances when one would desire to test theperformance of an ophthalmic lens in an ocular environment, other thanwhen said ophthalmic lens contains a pharmaceutical agent. For exampleif one wanted to determine whether surfactants, excipients,preservatives, wetting agents or other components of solutions (“eyecaresolution components”) were absorbed by the lens, it would be useful tohave a test that mimics the performance of the lens in an ocularenvironment. In light of this need this invention includes a method ofmeasuring the uptake rate of an eyecare solution component to anophthalmic lens, wherein the method comprises the steps of

-   -   (a) placing an ophthalmic lens in the testing area of an        apparatus comprising a male mold and a female mold,        -   wherein said male mold comprises a convex testing surface an            outer male surface, male seating ridge extending from the            perimeter of the convex testing surface, and an aperture            extending from said outer male surface to said convex            testing surface,        -   wherein said female mold comprises an outer female surface a            concave testing surface, female seating ridge extending from            the perimeter of the concave testing surface, and an            aperture extending from said concave testing surface to said            outer female surface,        -   wherein when the male mold and the female mold are mated,            the male seating ridge sits on the female seating ridge and            creates a testing area between the male convex testing            surface and the female concave testing surface.    -   (b) adding a solution comprising eyecare solution components to        the aperture of the male mold from the outer male surface, and    -   (c) monitoring the solution that emerges from the aperture of        the outer female surface to determine the presence or absence of        the eyecare solution component.        As used herein the term male mold, female mold, radial groove,        latitudinal groove, testing area convex testing surface, concave        testing surface, eyecare solution component, ophthalmic lens,        solution and monitoring are as described above.

The specific embodiments of the apparatuses and methods of the inventionillustrate, but do not limit the invention. They are meant only tosuggest a method of practicing the invention. Those knowledgeable incontact lenses as well as other specialties may find other methods ofpracticing the invention. However, those methods are deemed to be withinthe scope of this invention.

1. An apparatus for testing an ophthalmic lens comprising a male moldand a female mold, wherein said male mold comprises a convex testingsurface, an outer male surface, male seating ridge extending from theperimeter of the convex testing surface, and an aperture extending fromsaid outer male surface to said convex testing surface, wherein saidfemale mold comprises an outer female surface a concave testing surface,female seating ridge extending from the perimeter of the concave testingsurface, and an aperture extending from said concave testing surface tosaid outer female surface, wherein when the male mold and the femalemold are mated, the male seating ridge sits on the female seating ridgeand creates a testing area between the male convex testing surface andthe female concave testing surface.
 2. The apparatus of claim 1 whereinsaid convex testing surface comprises at least one radial grooveextending from the aperture to the perimeter of the convex testingsurface and at least one latitudinal groove that intersects the at leastone radial groove.
 3. The apparatus of claim 2 wherein the convextesting surface comprises at least four radial grooves.
 4. The apparatusof claim 2 wherein the convex testing surface comprises at least fourlatitudinal grooves.
 5. The apparatus of claim 1 wherein said concavetesting surface comprises at least one radial groove extending from theaperture to the perimeter of the concave testing surface and at leastone latitudinal groove that intersects the at least one radial groove,6. The apparatus of claim 5 wherein the concave testing surfacecomprises at least two radial grooves.
 7. The apparatus of claim 5wherein the concave testing surface comprises at least four latitudinalgrooves.
 8. The apparatus of claim 5 wherein the concave testing surfacecomprises at least four radial grooves.
 9. The apparatus of claim 2wherein said concave testing surface comprises at least one radialgroove extending from the aperture to the perimeter of the concavetesting surface and at least one latitudinal groove that intersects theat least one radial groove.
 10. The apparatus of claim 9 wherein theconvex testing surface comprises at least two radial grooves and atleast three latitudinal grooves and the concave surface comprises atleast two radial grooves and at least three latitudinal grooves. 11.(canceled)
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